Caterina Compostella

Association of HIV and ART with cardiometabolic traits in sub-Saharan Africa: a systematic review and meta-analysis

Background Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. Methods We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. Results Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, −0.59; 95% CI, −0.86 to −0.31), BMI (SMD, −0.32; 95% CI, −0.45 to −0.18), SBP (SMD, −0.40; 95% CI, −0.55 to −0.25) and DBP (SMD, −0.34; 95% CI, −0.51 to −0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, −0.34; 95% CI, −0.62 to −0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. Conclusions Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.

Exercise performance of chronic heart failure patients in the early period of support by an axial-flow left ventricular assist device as destination therapy.

Axial-flow left ventricular assist devices (LVADs) are increasingly used as destination therapy in end-stage chronic heart failure (CHF), as they improve survival and quality of life. Their effect on exercise tolerance in the early phase after implantation is still unclear. The aim of this study was to evaluate the effect of LVADs on the exercise capacity of a group of CHF patients within 2 months after initiation of circulatory support. Cardiopulmonary exercise test data were collected for 26 consecutive LVAD-implanted CHF patients within 2 months of initiation of assistance; the reference group consisted of 30 CHF patients not supported by LVAD who were evaluated after an episode of acute heart failure. Both LVAD and reference groups showed poor physical performance; LVAD patients achieved lower workload (LVAD: 36.3 ± 9.0 W, reference: 56.6 ± 18.2 W, P < 0.001) but reached a similar peak oxygen uptake (peak VO2 ; LVAD: 12.5 ± 3.0 mL/kg/min, reference: 13.6 ± 2.9 mL/kg/min, P = ns) and similar percentages of predicted peak VO2 (LVAD: 48.8 ± 13.9%, reference: 54.2 ± 15.3%, P = ns). While the values of the O2 uptake efficiency slope were 12% poorer in LVAD patients than in reference patients (1124.2 ± 226.3 vs. 1280.2 ± 391.1; P = ns), the kinetics of VO2 recovery after exercise were slightly better in LVAD patients (LVAD: 212.5 ± 62.5, reference: 261.1 ± 80.2 sec, P < 0.05). In the first 2 months after initiation of circulatory support, axial-flow LVAD patients are able to sustain a low-intensity workload; though some cardiopulmonary exercise test parameters suggest persistence of a marked physical deconditioning, their cardiorespiratory performance is similar to that of less compromised CHF patients, possibly due to positive hemodynamic effects beginning to be produced by the assist device.

A practical review for cardiac rehabilitation professionals of continuous-flow left ventricular assist devices: historical and current perspectives.

An increasing number of patients with end-stage heart failure are being treated with continuous-flow left ventricular assist devices (cf-LVADs). These patients provide new challenges to the staff in exercise-based cardiac rehabilitation (CR) programs. Even though experience remains limited, it seems that patients supported by cf-LVADs may safely engage in typical rehabilitative activities, provided that some attention is paid to specific aspects, such as the presence of a short external drive line. In spite of initial physical deconditioning, CR allows progressive improvement of symptoms such as fatigue and dyspnea. Intensity of rehabilitative activities should ideally be based on measured aerobic capacity and increased appropriately over time. Regular, long-term exercise training results in improved physical fitness and survival rates. Appropriate adjustment of cf-LVAD settings, together with maintenance of adequate blood volume, provides maximal output, while avoiding suction effects. Ventricular arrhythmias, although not necessarily constituting an immediate life-threatening situation, deserve treatment as they could lead to an increased rate of hospitalization and poorer quality of life. Atrial fibrillation may worsen symptoms of right ventricular failure and reduce exercise tolerance. Blood pressure measurements are possible in cf-LVAD patients only using a Doppler technique, and a mean blood pressure ⩽80 mmHg is considered “ideal.” Some patients may present with orthostatic intolerance, related to autonomic dysfunction. While exercise training constitutes the basic rehabilitative tool, a comprehensive intervention that includes psychological and social support could better meet the complex needs of patients in which cf-LVAD may offer prolonged survival.

History of erectile dysfunction as a predictor of poor physical performance after an acute myocardial infarction.

Background Erectile dysfunction may predict future cardiovascular events and indicate the severity of coronary artery disease in middle-aged men. The aim of this study was to evaluate whether erectile dysfunction (expression of generalized macro- and micro-vascular pathology) could predict reduced effort tolerance in patients after an acute myocardial infarction. Patients and methods One hundred and thirty-nine male patients (60 ± 12 years old), admitted to intensive cardiac rehabilitation 13 days after a complicated acute myocardial infarction, were evaluated for history of erectile dysfunction using the International Index of Erectile Function questionnaire. Their physical performance was assessed by means of two six-minute walk tests (performed two weeks apart) and by a symptom limited cardiopulmonary exercise test (CPET). Results Patients with erectile dysfunction (57% of cases) demonstrated poorer physical performance, significantly correlated to the degree of erectile dysfunction. After cardiac rehabilitation, they walked shorter distances at the final six-minute walk test (490 ± 119 vs. 564 ± 94 m; p < 0.001); at CPET they sustained lower workload (79 ± 28 vs. 109 ± 34 W; p < 0.001) and reached lower oxygen uptake at peak effort (18 ± 5 vs. 21 ± 5 ml/kg per min; p = 0.003) and at anaerobic threshold (13 ± 3 vs.16 ± 4 ml/kg per min; p = 0.001). The positive predictive value of presence of erectile dysfunction was 0.71 for low peak oxygen uptake (<20 ml/kg per min) and 0.69 for reduced effort capacity (W-max <100 W). Conclusions As indicators of generalized underlying vascular pathology, presence and degree of erectile dysfunction may predict the severity of deterioration of effort tolerance in post-acute myocardial infarction patients. In the attempt to reduce the possibly associated long-term risk, an optimization of type, intensity and duration of cardiac rehabilitation should be considered.

Cardiac autonomic dysfunction in the early phase after left ventricular assist device implant: Implications for surgery and follow-up

Purpose In congestive heart failure (CHF) patients, a profound cardiac autonomic derangement, clinically expressed by reduced heart rate variability (HRV), is present and is related to the degree of ventricular dysfunction. Implantation of a left ventricular assist device (LVAD) can progressively improve HRV, associated with an increased circulatory output. Data from patients studied at different times after LVAD implantation are controversial. The aims of this study were to assess cardiac autonomic function in the early phases after axial-flow LVAD implantation, and to estimate the potential relevance of recent major surgical stress on the autonomic balance. Methods HRV (time-domain; 24-h Holter) was evaluated in 14 patients, 44.8 ± 25.8 days after beginning of Jarvik-2000 LVAD support; 47 advanced stage CHF, 24 cardiac surgery (CS) patients and 30 healthy subjects served as control groups. Inclusion criteria: sinus rhythm, stable clinical conditions, no diabetes or other known causes of HRV alteration. Results HRV was considerably reduced in LVAD patients in the early phases after device implantation in comparison to all control groups. A downgrading of HRV parameters was also present in CS controls. Circadian oscillations were highly depressed in LVAD and CHF patients, and slightly reduced in CS patients. Conclusions In CHF patients supported by a continuous-flow LVAD, a profound cardiac dysautonomia is still evident in the first two months from the beginning of circulatory support; the degree of cardiac autonomic imbalance is even greater in comparison to advanced CHF patients. The recent surgical stress could be partly linked to these abnormalities.

Does heart rate variability correlate with long-term prognosis in myocardial infarction patients treated by early revascularization?

AIM To assess the prevalence of depressed heart rate variability (HRV) after an acute myocardial infarction (MI), and to evaluate its prognostic significance in the present era of immediate reperfusion. METHODS Time-domain HRV (obtained from 24-h Holter recordings) was assessed in 326 patients (63.5 ± 12.1 years old; 80% males), two weeks after a complicated MI treated by early reperfusion: 208 ST-elevation myocardial infarction (STEMI) patients (in which reperfusion was successfully obtained within 6 h of symptoms in 94% of cases) and 118 non-ST-elevation myocardial infarction (NSTEMI) patients (percutaneous coronary intervention was performed within 24 h and successful in 73% of cases). Follow-up of the patients was performed via telephone interviews a median of 25 mo after the index event (95%CI of the mean 23.3-28.0). Primary end-point was occurrence of all-cause or cardiac death; secondary end-point was occurrence of major clinical events (MCE, defined as mortality or readmission for new MI, new revascularization, episodes of heart failure or stroke). Possible correlations between HRV parameters (mainly the standard deviation of all normal RR intervals, SDNN), clinical features (age, sex, type of MI, history of diabetes, left ventricle ejection fraction), angiographic characteristics (number of coronary arteries with critical stenoses, success and completeness of revascularization) and long-term outcomes were analysed. RESULTS Markedly depressed HRV parameters were present in a relatively small percentage of patients: SDNN < 70 ms was found in 16% and SDNN < 50 ms in 4% of cases. No significant differences were present between STEMI and NSTEMI cases as regards to their distribution among quartiles of SDNN (χ2 =1.536, P = 0.674). Female sex and history of diabetes maintained a significant correlation with lower values of SDNN at multivariate Cox regression analysis (respectively: P = 0.008 and P = 0.008), while no correlation was found between depressed SDNN and history of previous MI (P = 0.999) or number of diseased coronary arteries (P = 0.428) or unsuccessful percutaneous coronary intervention (PCI) (P = 0.691). Patients with left ventricle ejection fraction (LVEF) < 40% presented more often SDNN values in the lowest quartile (P < 0.001). After > 2 years from infarction, a total of 10 patients (3.1%) were lost to follow-up. Overall incidence of MCE at follow-up was similar between STEMI and NSTEMI (P = 0.141), although all-cause and cardiac mortality were higher among NSTEMI cases (respectively: 14% vs 2%, P = 0.001; and 10% vs 1.5%, P = 0.001). The Kaplan-Meier survival curves for all-cause mortality and for cardiac deaths did not reveal significant differences between patients with SDNN in the lowest quartile and other quartiles of SDNN (respectively: P = 0.137 and P = 0.527). Also the MCE-free survival curves were similar between the group of patients with SDNN in the lowest quartile vs the patients of the other SDNN quartiles (P = 0.540), with no difference for STEMI (P = 0.180) or NSTEMI patients (P = 0.541). By the contrary, events-free survival was worse if patients presented with LVEF < 40% (P = 0.001). CONCLUSION In our group of patients with a recent complicated MI, abnormal autonomic parameters have been found with a prevalence that was similar for STEMI and NSTEMI cases, and substantially unchanged in comparison to what reported in the pre-primary-PCI era. Long-term outcomes did not correlate with level of depression of HRV parameters recorded in the subacute phase of the disease, both in STEMI and in NSTEMI patients. These results support lack of prognostic significance of traditional HRV parameters when immediate coronary reperfusion is utilised.

Functional parameters but not heart rate variability correlate with long-term outcomes in St-elevation myocardial infarction patients treated by primary angioplasty

BACKGROUND Depressed heart rate variability (HRV) is usually considered a negative long-term prognostic factor after acute myocardial infarction. Anyway, most of the supporting research was conducted before the era of immediate reperfusion by percutaneous coronary intervention (PCI). Main aim of this study was to evaluate if HRV still retains prognostic significance in our era of immediate PCI. METHODS AND RESULTS Two weeks after STEMI treated by primary PCI, time-domain HRV was assessed from 24-h Holter recordings in 186 patients: markedly depressed HRV (SDNN <70ms or <50ms) was present in 16% and in 5% of cases, respectively; patients with left ventricle ejection fraction (LVEF) <40% presented more often SDNN values in the lowest quartile. Physical performance was also assessed, by 6-minute walk tests (6MWT) and by cardiopulmonary exercise test (CPET). After >2years from infarction, occurrence of major clinical events (MCE) was investigated. Cases with or without MCE did not differ by initial HRV parameters; Kaplan-Meier events-free survival curves were similar between patients with lowest quartile SDNN and the remaining ones (χ2 0.981, p=0.322). By the contrary, events-free survival was worse if patients walked shorter distances at 6MWT (χ2 6.435, p=0.011), developed poorer ventilatory efficiency at CPET (χ2 10.060, p=0.002), or presented LVEF <40% (χ2 7.085, p=0.008). CONCLUSIONS In primary-PCI STEMI patients, markedly abnormal HRV was found in a small percentage of cases. HRV seems to have lost its prognostic significance, while parameters indicating LV function (LVEF and physical performance) could allow better prognostication in primary-PCI STEMI patients.

Abnormal heart rate variability and atrial fibrillation after aortic surgery.

Introduction Complete denervation of transplanted heart exerts protective effect against postoperative atrial fibrillation; various degrees of autonomic denervation appear also after transection of ascending aorta during surgery for aortic aneurysm. Objective This study aimed to evaluate if the level of cardiac denervation obtained by resection of ascending aorta could exert any effect on postoperative atrial fibrillation incidence. Methods We retrospectively analysed the clinical records of 67 patients submitted to graft replacement of ascending aorta (group A) and 132 with aortic valve replacement (group B); all episodes of postoperative atrial fibrillation occurred during the 1-month follow-up have been reported. Heart Rate Variability parameters were obtained from a 24-h Holter recording; clinical, echocardiographic and treatment data were also evaluated. Results Overall, 45% of patients (group A 43%, group B 46%) presented at least one episode of postoperative atrial fibrillation. Older age (but not gender, abnormal glucose tolerance, ejection fraction, left atrial diameter) was correlated with incidence of postoperative atrial fibrillation. Only among a subgroup of patients with aortic transection and signs of greater autonomic derangement (heart rate variability parameters below the median and mean heart rate over the 75th percentile), possibly indicating more profound autonomic denervation, a lower incidence of postoperative atrial fibrillation was observed (22% vs. 54%). Conclusion Transection of ascending aorta for repair of an aortic aneurysm did not confer any significant protective effect from postoperative atrial fibrillation in comparison to patients with intact ascending aorta. It could be speculated that a limited and heterogeneous cardiac denervation was produced by the intervention, creating an eletrophysiological substrate for the high incidence of postoperative atrial fibrillation observed.

Impact of type of intervention for aortic valve replacement on heart rate variability

BACKGROUND It is known that coronary heart surgery leads to varying degrees of cardiac autonomic derangement, clinically detectable as depression of heart rate variability (HRV) parameters. Few studies report that also surgical replacement of the aortic valve (SAVR) may lead to HRV abnormalities, while very little is known about the autonomic effects obtained after less invasive aortic valve replacement techniques. The study aimed to evaluate HRV after SAVR and to compare it with two less invasive techniques, transapical (TaAVI) and tranfemoral (TfAVI) aortic valve implant. METHODS Time-domain heart rate variability (HRV) parameters have been studied by 24-h Holter ECG in 129 patients after SAVR, in 63 patients after TfAVI and in 19 patients after TaAVI. RESULTS All HRV parameters were significantly depressed in SAVR, while they were almost completely preserved in TfAVI patients; TaAVI cases showed a somehow intermediate behaviour [(SDNN respectively: 71.0±34.9 vs 95.9±29.5 (p<0.001) vs 84.4±32.6ms (p=ns)]. Mean heart rate during the 24-h Holter was 8% higher in SAVR patients than in both TfAVI and TaAVI patients. The reported results were not correlated with echocardiographic ejection fraction, or presence of abnormal glucose metabolism, or degree of anaemia or treatment with beta-blockers. CONCLUSIONS SAVR leads to profound depression of some cardiac autonomic parameters, while less invasive procedures allow better preservation of HRV. In particular TfAVI does not induce any significant deterioration of HRV parameters and seems to be the strategy of valve implant with less impact on the cardiovascular autonomic system.

HIV treatment is associated with a twofold higher probability of raised triglycerides: Pooled analyses in 21 023 individuals in sub-Saharan Africa

Background Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TGs) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. Methods Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. Findings Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51–2.77, I2 = 45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. Interpretation Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.